The present invention relates to an accommodating intraocular lens and to an injectable composition of polysiloxanes having suitable characteristics form an accommodating lens.
The human eye is a highly evolved and complex sensory organ. It is composed of a cornea, or clear outer tissue which refracts light rays enroute to the pupil, an iris which controls the size of the pupil thus regulating the amount of light entering the eye, and a lens which focuses the incoming light through the vitreous fluid to the retina. The retina converts the; incoming light into electrical energy that is transmitted through the brain stem to the occipital cortex resulting in a visual image. In the perfect eye the light path from the cornea, through the lens and vitreous fluid to the retina is unobstructed. Any obstruction or loss in clarity within these structures causes scattering or absorption of light rays resulting in diminished visual acuity. For example, the cornea can become damaged resulting in oedema, scarring or abrasions, the lens is susceptible to oxidative damage, trauma and infection, and the vitreous can become cloudy due to hemorrhage or inflammation.
As the body ages, the effects of oxidative damage caused by environmental exposure and endogenous free radical production accumulate resulting in a loss of lens flexibility and denatured proteins that slowly coagulate reducing lens transparency. The natural flexibility of the lens is essential for focusing light onto the retina by a process referred to as accommodation. Accommodation allows the eye to automatically adjust the field of vision for objects at different distances. A common condition known as presbyopia results when the cumulative effects of oxidative damage diminish this flexibility reducing near vision acuity. Presbyopia usually begins to occur in adults during their mid-forties; mild forms are treated with glasses or contact lenses.
Lenticular cataract is a lens disorder resulting from the further development of coagulated protein and calcification. There are four common types of cataracts: senile cataracts associated with aging and oxidative stress, traumatic cataracts which develop after a foreign body enters the lens capsule or following intense exposure to ionizing radiation or infrared rays, complicated cataracts which are secondary to diseases such as diabetes mellitus or eye disorders such as detached retinas, glaucoma and retinitis pigmentosa, and toxic cataracts resulting from medicinal or chemical toxicity. Regardless of the cause, the disease results in impaired vision and may lead to blindness.
Treatment of severe lens disease requires the surgical removal of the lens involving phakoemulsification followed by irrigation and aspiration. However, without a lens the eye is unable to focus the incoming light on the retina. Consequently, an artificial lens is used to restore vision. Three types of prosthetic lenses are available: cataract glasses, external contact lenses and IOLs. Cataract glasses have thick lenses, are uncomfortably heavy and cause vision artifacts such as central image magnification and side vision distortion. Contact lenses resolve many of the problems associated with glasses, but require frequent cleaning, are difficult to handle (especially for elderly patients with symptoms of arthritis), and are not suited for persons who have restricted tear production. Intraocular lenses are used in the majority of cases to overcome the aforementioned difficulties associated with cataract glasses and contact lenses.
IOLs mentioned in the prior art literature usually belong to one of the following categories: non-deformable, foldable, expansible hydrogels and injectable. The earliest IOLs coming into surgical practice are non-deformable implants having rigid structures composed of acrylates and methacrylates. This type of lenses requires a large surgical incision in the capsular bag and is not accommodative. The large incision results in protracted recovery times and the likelihood of introducing astigmatism. In an effort to reduce recovery time and patient discomfort numerous small incision techniques and lenses have been developed.
Present IOLs designed for small incision implantation have elastomeric characteristics and can be made of silicone materials. This type of lenses can be rolled or folded, inserted into the capsular sac then unfolded once inside. Occasionally, the folding of the lens before insertion results in permanent deformation adversely effecting the implant""s optical qualities. Foldable lenses meet the requirement of reducing the large surgical incision non-deformable lenses required, but are not accommodative. Moreover, both non-deformable and foldable IOLs are susceptible to mechanical dislocation resulting in damage to the corneal endothelium.
It has further been suggested to use an elastomeric polymer that becomes pliable when heated to body temperature or slightly above in small incision IOL implantation. Once pliable, such a lens would be deformed along at least one axis reducing its size sufficient for easy insertion through a small incision. The lens is then cooled to retain the modified shape until reheated. The cooled lens is inserted into the capsular sac and the natural body temperature warms the lens and it returns to its original shape. The primary drawback to the thermoplastic lens is the limited number of polymers that meet the exacting needs of this approach. Most polymers are composed of polymethylacrylate which have solid-liquid transition temperatures above 100xc2x0 C. To reduce these transition temperatures modifications of the polymer substrate with the use of plasticizers is required which eventually may leach into the eye.
Dehydrated hydrogels have also been suggested for small incisions techniques. Hydrogel lenses are dehydrated before insertion and naturally rehydrated once inside the capsular sac. However, once fully rehydrated the polymer structure is notoriously weak due to the large amount of water absorbed. The typical dehydrated hydrogel""s diameter will expand from 3 mm to 6 mm resulting in a lens that contains about 85% water. At this water concentration the refractive index drops to approximately 1.36 which is unacceptable for an IOL. To achieve a refractive index equal or greater than that of the natural lens ( greater than 1.40) a significantly thicker lens is required; this is even further exacerbated when lens diameters exceed 6 mm.
To further develop IOLs and reduce surgical incisions to below 1.5 mm, techniques with injectable IOLs have been suggested, wherein the low viscosity lens material is directly injected into the empty capsular bag and cured in situ as a part of the surgical procedure. In this process the capsular bag is to be used as a mold to form the shape of the lens and thereby contribute control its refraction. There have been several attempts to develop materials suitable for use as injectable IOLs. For example, Gerace et al. describe a fast curing mixture of vinyl-containing polyorganosiloxanes, organosilicone comprising hydride groups and a platinum group metal catalyst used to form an IOL in their U.S. Pat. Nos. 5,278,258, 5,391,590 and 5,411,553 patents. The resulting polymers demonstrate a reduced tendency of discoloration compared to other platinum catalyzed silicone polymers. The ""590 patent also discloses a substantially non-functional polymer component of the mixture that has a viscosity at least 50 times greater than the functional polymers. The non-functional component is mixed with the functional components to adjust viscosity to a pre-determined specification. Apart from problems with obtaining control over the crosslinking process and finding clinically acceptable conditions, there has been a struggle to perfect the polyorganosiloxane compositions, since they need to have a suitable viscosity for injection, a suitably high refractive index as well as suitable mechanical characteristics after crosslinking, i.e. a suitable modulus. Polydimethylsiloxane (PDMS) has been employed as a material in foldable IOLs and has refractive index similar to that of the natural crystalline lens. This material is also exemplified as a part of the injection mixture in the above-mentioned patents to Gerace et al. PDMS has also been found to have a relatively low viscosity and thereby a tendency to leak out of the desired injection site (i.e. the capsular bag). This is considered in the mentioned U.S. Pat. No. 5,391,590, wherein an additional high viscosity polysiloxane is added to the injection mixture. However, high viscosity silicones have the drawback in that they can entrap air bubbles, which can impair the optical quality of the resulting product. In addition, it has been found that polyorganosiloxanes having a high fraction of dimethylsiloxane units may have an unacceptable low specific gravity with the undesired result that the injected lens material will float on an aqueous layer in the capsular bag. In such a case, it will be difficult to fill the capsular sac completely and requires the surgeon to manually express water in order to maintain the correct lens shape during the curing process. The International Patent Application PCT/EP99/07780 discloses improved polysiloxane terpolymers which have improved characteristics in terms of refractive index, density and viscosity, when compared to the earlier mentioned polysiloxanes. A functionalized form of this type of polysiloxanes is well suited to be part of a thermocurable injectable composition together with a crosslinker and a catalyst. Functional polysiloxanes in this context means that it is provided with functional groups for crosslinking. In a thermocurable system, this typically means that vinyl end groups (xe2x80x9cvinyl cappingxe2x80x9d) are introduced on the polymer chain, which can form a crosslinked network with hydride groups on the crosslinker in the presence of the catalyst at given temperature. The International Patent Application PCT/EP99/07781 discloses similar polysiloxane terpolymers which are functionalized with acrylic groups to be suitable for an injectable photocurable composition together with a photoinitiator.
The mentioned polysiloxane terpolymers are capable of solving a number of technical problems related to the preparation of intraocular lenses in-situ in the capsular bag with an injectable composition of functionalized polysiloxanes. However, there is still a need for an injectable polysiloxane material which could form an intraocular lens with sufficiently low elasticity modulus so the lens can undergo accommodation by the forces of the eye. In practical terms this would mean that a lens formed by the polysiloxane material should have a Young""s modulus less than 10 kPa and preferably less than about 5 kPa. The purpose of the present invention is to provide improved injectable polysiloxane compositions which admit control of the elasticity modulus of a resulting product, i.e. an intraocular lens implanted with an injection method.
The objects of the present invention are to provide an injectable composition capable of preparing an accommodating intraocular lens directly in the capsular bag of the eye from which an impaired natured lens has been surgically removed. An accommodating lens is defined as lens having a sufficiently low elasticity so it can undergo accommodation under the influence of the eye muscles normally used for the natural lens. This means that the implanted lens resulting from the inventive injectable composition must have a Young""s modulus approaching the low value of about 1 kPa of the natural lens. Preferably the inventive compositions can provide lens with as low values as below 10 kPa or even below about 5 kPa which are regarded as clinical conceivable values to restore the accommodation of the patient. It is also an object of the present invention to provide injectable compositions that will form an accommodating lens with a stabilized Young""s modulus. This means that the lens has a sufficiently constant Young""s implant intraocular lens formed from the injected material.
In its most general form the present invention relates to a composition of polysiloxanes in an injectable ophthalmically acceptable form having a specific gravity of greater than about 1.0, a refractive index suitable for restoring the refractive power of the natural crystalline lens and a viscosity suitable for injection through a standard cannula.
The polysiloxanes of the composition have an refractive index ranges between 1.382 and up to about 1.60, preferably between from about 1.38 to 1.46 and more preferably index ranges from about 1.38 to 1.43, in order to be suitable as a material for the production of intraocular lenses. Most preferably, the inventive polysiloxanes have a specific gravity within the range of about 1.03 to about 1.20. The polysiloxanes should also have a suitable viscosity to be readily injectable through conventional cannula having an 18 Gauge needle dimension or finer dimensions. Preferably, the polysiloxanes should be able to pass through a 21 Gauge needle and more preferably through 25 Gauge needle. To meet with the requirement of being injectable, polysiloxanes according to the present invention have a viscosity less than about 60 000 cSt or preferably less than 5000 cSt. More preferably, the viscosity should be less than about 1500 cSt, wherein the mentioned viscosity values are given at room temperature. The skilled person will be able to relate these requirements to suitable degrees of polymerization.
The polysiloxanes typically consist essentially of different siloxane monomer units having the general formula xe2x80x94RaRbSiOxe2x80x94, wherein Ra and Rb are the same or different substituted or unsubstituted alkyl or aryl groups bound to the silicone atom. In accordance with the present invention, at least one of the siloxane monomers included in the polysiloxanes has specific gravity greater than about 1.0. According to one aspect of the invention the polysiloxanes has at least one monomer, wherein Ra and Rb are the same or different alkyl or aryl groups of which at least one of said groups is substituted with one or several fluorine atoms. Preferably, the polysiloxanes comprises monomer units, wherein Ra is fluoroalkyl and Rb is alkyl and most preferably the polysiloxanes comprise 3,3,3-trifluoropropylmethylsiloxane monomers. In order to provide the polysiloxanes with the typically high specific gravity, it is preferred that the amount of fluoroalkyl containing monomers exceed about 4 mol %. Further, it is also preferable that one of the siloxane monomers is an arylsiloxane and especially preferred arylsiloxanes are diphenylsiloxane and phenylalkylsiloxane.
In one suitable embodiment, the polysiloxanes of the composition essentially are terpolymers derived from three different siloxane monomers of the general formula (R1R2SiO)1 (R3R4SiO)m(R5R6SiO), wherein one of the three monomers has a specific gravity greater than about 1.0 and said terpolymer has a refractive index of about 1.41. In order to accomplish polysiloxanes with the mentioned requirements which the inventors have found to be advantageous for obtaining a material suitable for being injected into the capsular bag of the eye, it has been found suitable that R1 and R2 are the same or different lower substituted or unsubstituted alkyl and most preferable both are methyl. R3 and R4 shall be selected among the same or different substituted or unsubstituted aryl and alkyl groups, preferably R3 is phenyl and R4 is phenyl or methyl. R5 and R6 shall be selected among fluoroalkyl and alkyl groups and preferably R5 is trifluoropropyl and R6 is methyl. Alternatively, the inventive polysiloxanes can be higher polymers than terpolymers including but not limited to tetracopolymers with the same monomer types as mentioned.
According to one especially suitable embodiment the, polysiloxanes of the composition essentially are terpolymers having the formula: 
wherein R1 and R2 are independently C1-C6 alkyl; R3 is phenyl; R4 is phenyl or C1-C6alkyl; R5 is CF3(CH2)x wherein x is 1-5; R6 is C1-C6 alkyl or fluoroalkyl; 1 is in the molar fraction range of 0 to 0.95; m is in the molar fraction range of 0 to 0.7; and n is in the molar fraction range of 0 to 0.65. It is preferred that R1 is methyl, that R2 is methyl, R4 is phenyl, that x is 2, either independently, or in combination. Preferably according to these alternatives R6 is methyl. According to one embodiment, the polysiloxane is a copolymer of diphenyl or phenylalkyl siloxane and dialkyl siloxane. According to further embodiments, the polysiloxane is a copolymer of diphenyl or phenylalkyl siloxane and trifluoroalkyl(alkyl)siloxane, or a terpolymer or higher order polymer of diphenyl and/or phenylalkyl siloxane, dialkyl siloxane and trifluoroalkyl alkyl siloxane. According to a specific preferred embodiment, the polysiloxane is a terpolymer of dimethyl siloxane, diphenyl siloxane or phenylmethyl siloxane and 3,3,3-trifluoropropylmethyl siloxane. Preferably, said polysiloxanes comprise at least about 4 mol % of trifluoropropylmethyl siloxane and 1 to 50 mol % of diphenylsiloxane and/or phenylmethylsiloxane. More preferably said polysiloxanes comprise about 4 to 65 mol % 3,3,3 trifluoropropylmethyl siloxane, 1 to 50 mol % of diphenylsiloxane and dimethylsiloxane monomer units. One suitable polysiloxane composition for being a part of a composition for injection into the capsular bag of the human eye for the formation of IOL comprises about 28 mol % trifluoropropylmethyl siloxane, about 4 mol % diphenyl siloxane and dimethyl siloxane monomer units.
In accordance with the present invention it has been found that a suitable Young""s modulus is obtainable with the inventive polysiloxane compositions after a crosslinking process with functional forms of the polysiloxanes and a multifunctional hydride crosslinking agent, if appropriate considerations are taken to the relative of amounts functional polysiloxanes and multifunctional hydride crosslinking agent. The functional polysiloxanes preferably are functionalized to contain vinyl groups capable of participating in a crosslinking reaction with hydride groups of the crosslinking agent. Functional groups for crosslinking will in the context of the present invention in a general sense include unsaturated groups suitable for reaction with silicone bonded hydride (Sixe2x80x94H) groups in the presence of a catalyst, i.e. thermocuring. The skilled person can identify a large number of different alkenyl moieties and different routes of how to synthesize e.g. vinyl functional polysiloxanes. A suitable and commonly employed route is to introduce end-blocking groups of vinyldimethyl siloxane wherein the olefinic vinyl group will enable curing by crosslinking. Alternatively, the functional groups will include acrylic groups capable of participating in a different type of crosslinking reaction induced by a photoinitiator as is disclosed in PCT/EP99/07781, which hereby is incorporated as a reference. The crosslinking agents are of the siloxane or polysiloxane (i.e. a multifunctional organohydrogenpolysiloxane) type carrying at least two, preferably at least three Sixe2x80x94H groups, as disclosed in U.S. Pat. Nos. 5,278,258 and 5,444,106 which documents are incorporated as general references for the crosslinking process. Other suitable crosslinkers are the branched siloxanes mentioned in U.S. Pat. No. 2,877,255. The catalysts can be found among platinum group metal containing catalysts commonly employed for catalyzing the formation of bonds between Sixe2x80x94H groups and vinyl groups as referred to in U.S. Pat. No. 5,278,258. A first suitable crosslinking agent is selected among tetrafunctional crosslinking agents, i.e. those having four hydride groups. An example of a particularly suitable crosslinking agent for the present invention is tetrakis(dimethylsiloxy)silane. A second type of suitable crosslinking agents are difunctional crosslinking agents, i.e. those having two hydride groups. It is to be understood that compositions including crosslinkers with different numbers of functionality (i.e. different amounts of hydride groups per molecule) can be included in the inventive compositions to control the Young""s modulus of the final product.
According to a preferred embodiment the crosslinking agent comprises a tetrafunctional crosslinker.
In a first example of this embodiment the polysiloxanes are in a comparatively excessive amount to the crosslinking agent, such that the total amount of functional groups for crosslinking of the polysiloxanes exceeds the number of functional groups participating for the crosslinking process of the crosslinking agent. Suitably this means that the number of vinyl groups of polysiloxanes exceeds the number of hydride groups (Sixe2x80x94H bonds) available on the crosslinkers. After conducting the crosslinking reaction, a fraction of functional polysiloxanes will be unreacted and not be a part of crosslinked network. These polysiloxanes will be able to act as a plasticiser, which modulates the elasticity modulus of a final intraocular lens product.
In a second example of this embodiment, the crosslinking agent is in excess so that an excess of hydride to vinyl bonds is provided. According to this aspect, a fraction of the crosslinking agent rather acts as a chain extender and thereby contribute to a looser more lightly crosslinked network.
In order to safely maintain a stabilized Young""s modulus, it has been found necessary to avoid postcuring. Postcuring is a slow process that occurs after the initial fast gellation process has finished and is especially pronounced when an excess of hydride to vinyl groups are used in the crosslinking process, see X Quan in Polymer Engineering and Sci., 1988, 29(20), 1419-1425. In order to overcome postcuring it is therefor preferred to have an excess of vinyl groups over hydride groups in the injectable composition.
In accordance with both these examples, the Young""s modulus of the resulting crosslinked product can be reduced in a controlled manner by adding an amount of non-functional polysiloxanes free from functional groups for crosslinking to the compositions. Non-functional groups are defined herein as groups incapable of participating in a crosslinking reaction. Typically a non-functional polysiloxane in accordance with present invention may have end groups of trimethylsiloxane. Advantageously, the functional and non-functional polysiloxanes are compatible to each other in terms of structure, so they are sufficiently miscible in a mixture. Structural differences of the polysiloxanes of the inventive composition may scatter light and appear hazy, misty or opaque rendering them unsuitable for optical applications. Preferably, the functional and non-functional polysiloxanes essentially are the same polysiloxane of the groups being defined above, i.e. most preferably essentially the same terpolymer. A composition of functional and non-functional polysiloxanes will further comprise a crosslinking agent capable of reacting with the functional groups of the polysiloxanes an effective amount of a catalyst so as to cure the composition at a suitable temperature into a final product. The resulting crosslinked composition will have a network formed by the functional polysiloxanes and the crosslinking agent within which the non-functional polysiloxanes are distributed and will act as a plasticizer for the product. The non-functional polysiloxanes have the effect of swelling the network and increasing the space between the crosslinks. Considering the risk of diffusion of the non-functional polysiloxanes from an in-situ cured intraocular lens through the capsular bag into surrounding eye, these polymers are preferably selected with sufficiently high a molecular weight so as to substantially prevent from any such diffusion. Since there is a relation between molecular weight, polysiloxane viscosity and injectability of the composition, considerations must be taken to that an increase in the non-functional polysiloxane molecular weight does not compromise the overall viscosity of the composition in a way so it no longer readily can be injected with a standard cannula as outlined above: In one aspect of this embodiment, the viscosity of the non-functional polysiloxanes does not exceed the viscosity of the polysiloxanes having functional groups for crosslinking. In accordance with this aspect, one fraction of the polysiloxanes manufactured to be included in the composition can be provided with functional vinyl groups (e.g. vinyl end-capped), while the other fraction is included in its non-functionalized form. By conducting tests in vitro human capsular bag tissue, it has been found that the non-functional polysiloxanes preferably shall have molecular weight exceeding a value of about Mn=5000 g/mol to substantially reduce the risk of diffusion of such polysiloxanes from the capsular bag. Preferably, the molecular weight shall exceed Mn=7000 g/mol and even more preferably exceeding about 10000 g/mol.
In accordance with a specific example of the invention, the composition comprises non-functional polysiloxanes in excess to functional polysiloxanes. In this example the functional groups are vinyl groups and the relative amount of functional polysiloxanes to crosslinking agent in the composition is selected such that a relationship between hydride groups to vinyl groups is provided is 0.8:1, or with larger excess of vinyl groups. Suitably, the polysiloxanes are terpolymers of the structures defined according to above. Typical values for when using a tetrafunctional crosslinking agent are 50% to 93% (wt) non-functional polysiloxane and values within a similar range. For this type of compositions, the resulting elasticity modulus can be controlled by modifying the quantitative relationship between functional and non-functional polysiloxane and between the functional polysiloxane and the crosslinker.
One composition found to provide a suitable Young""s modulus below 5 kPa shortly after crosslinking includes a polysiloxane constituent of about 20% poly(dimethyl-co-diphenyl-co-trifluoropropylmethyl)siloxane terpolymer functionalized with vinyl groups (i.e. end-capped) and about 80% non-functional terpolymer of the same structure, tetrakis(dimethylsiloxy)silane as crosslinker in an amount such that a relationship of hydride to vinyl bonds of about 1.8:1 is obtained and a platinum metal catalyst.
Another composition found to provide a suitably stable Young""s modulus below about 5 kPa without postcure includes a polysiloxane constituent of about 20% poly(dimethyl-co-diphenyl-co-trifluoropropylmethyl)siloxane terpolymer functionalized with vinyl groups (i.e. end-capped) and about 80% non-functional terpolymer of the same structure, tetrakis(dimethylsiloxy)silane as crosslinker in an amount such that a relationship of hydride to vinyl bonds of about 0.8:1 is obtained and a platinum metal catalyst.
An alternative manner of obtaining a controlled reduction of the Young""modulus according to the present invention is to further comprise a difunctional crosslinker (i.e. a difunctional hydride) to the tetrafunctional crosslinker. An addition of difunctional (hydride) crosslinker is applicable on the composition discussed above. For example, a composition comprising functional polysiloxane and tetrafunctional crosslinker in amounts such that functional vinyl to hydride bonds has molar relationship of 1:1 or close to 1 (the number vinyl and hydride matches each other) will provide a substantially complete crosslinking reaction, since substantially every polysiloxane and crosslinker molecule will be attached to the network. In such a composition the obtainable Young""s modulus will be at its maximum, or close thereto. For this type of composition, a controlled reduction of the Young""s modulus is obtained by adding a fraction of difunctional crosslinker to the composition of tetrafunctional crosslinker. The difunctional crosslinker preferably is a short chain polydimethylsiloxane chain with hydride groups in its ends, which will act as a chain extender during the crosslinking. The addition of a difunctional crosslinker is a suitable alternative or complement to adding non-functional polysiloxanes as a means to obtain a controlled Young""s modulus reduction of crosslinked articles prepared with the inventive compositions, since it reduces the risk of free extractable polysiloxanes not being a part of network.
Within the general concept of the present invention it is possible to modify and control the Young""s modulus by changing the amount vinyl to hydride groups (i.e. the relative amount of functional polysiloxane to multifunctional hydride crosslinking agent), the concentration of non-functional polysiloxane and adding a chain extender (i.e. a difunctional hydride crosslinking agent. Post curing effect can be prevented by a skilled person by selecting appropriate compositions according to the invention and thereby ensuring stable material properties. The skilled person will readily identify combinations of these alternatives and when it is applicable.
According to an alternative embodiment of the invention, the polysiloxane composition may comprise only non-functional polysiloxanes. The non-functional polysiloxanes are selected among the same polysiloxanes as defined above with a preference for the terpolymers.
It is to be understood by the skilled person that the compositions are prepared by mixing a formulation of polysiloxanes and catalyst with a formulation of the crosslinking agent, just prior to its use. It is also to be understood that compositions can comprise further conventional constituents, such as agents for affecting the crosslinking and agents commonly associated with the production of IOLs from silicone materials, e.g. UV light absorbers.
Examples of preferred routes to produce the polysiloxanes of the inventive compositions and how to produce intraocular lenses from these compositions are given below.
The types of siloxane monomers useful in preparing the IOLs of this preferred embodiment include, but are not limited to, methyl and substituted methyl siloxanes, phenyl siloxanes and trifluoropropyl methyl siloxanes with individual specific gravities ranging between 0.97 and 1.28. The high specific gravity silicone copolymers of the present invention are prepared by mixing a plurality of these compounds in a predetermined ratio to achieve a desired specific gravity and refractive index.
According to one embodiment, three siloxane monomers are mixed together with a suitable end blocker and dried in a reduced atmosphere under controlled thermal conditions. The reaction mixture is then catalyzed to induce copolymerization in an inert atmosphere. The reaction is allowed to continue for a predetermined time in a precise thermal environment then terminated. Next, the reaction product is washed, precipitated and dried. The specific gravity, refractive index and mean molecular weight are determined.
In another embodiment of the present invention three siloxane monomers are mixed together with a suitable end blocker and dried in a reduced atmosphere under controlled thermal conditions as before. The reaction mixture is then catalyzed to induce copolymerization in an inert atmosphere. The reaction is allowed to continue for a predetermined time in a precise thermal environment then terminated. Next, the reaction product is washed, precipitated and dried. The resulting precipitate is then re-dissolved in a suitable solvent and filtered to enhance clarity. The specific gravity, refractive index and mean molecular weight are determined. Changes in the reactants, their relative concentrations and reaction conditions will result in a variety of end products with different specific gravities and refractive indices. The benefits of these differences will become apparent to one skilled in the art from the specific examples below.
According to the methods of the present invention, the ratio of siloxane monomer reactants necessary to achieve a desired refractive index and specific gravity can be approximated mathematically. If N is the desired IOL""s refractive index and P is the specific gravity of the lens"" copolymer and where n1-3 are the refractive indices and p1-3 are the specific gravities of the monomer reactants then the following mathematical relationship can be used:
N=x1n1+x2n2+x3n3
P=x1p1+x2p2+x3p3
Where x1-3 represent the ratio of the individual siloxane monomer reactants required to achieve an IOL with the desired optical and physical properties and x1+x2+x3=1.
Having an injectable silicone lens with a specific gravity greater than 1.0 will greatly simplify the injection process and represents a significant improvement over previously suggested materials for injectable lens materials. Prosthetic lenses made by the process described herein are compliant and retain the refractive index of the natural lens making them ideal as corrective lenses as well as replacements for damaged and cataractous lenses.
The present invention improves considerably on previously suggested polysiloxane based materials for injectable IOLs due to its increased specific gravity to above 1.0, so displace residual water after its injection into the capsular sac""s aqueous environment. This characteristic will reduce post-injection manipulation of the surgeon and will assure that the lens will assume a natural position and configuration. In accordance with the methods of the present invention an injectable IOL material is formed that greatly simplifies the injection, positioning and curing process. By the mentioned selection of siloxane monomers a high density injectable material can be provided with a controlled suitable refractive index comparable to that of the natural lens without compromising the other important requirements including a viscosity suitable for injection. This will greatly contribute to that is possible to adjust the refractive outcome of the injected lens formed with the capsular bag as a mold by having suitable fractions of siloxane units contributing to a high refractive index and siloxane units contributing to a high density. Another advantage of this invention is that extremely compliant nature fully cured lenses can be obtained. If a conventional foldable silicone lens is considered to have a stiffness of 100, a cured injectable lens made from the material of the present invention could be designed to have a stiffness ranging from zero to five. Therefore, lenses made from the material described herein can be accommodative and respond naturally to the changes in the eyes"" shape as focal length is adjusted. The accommodative nature of lenses fabricated from materials of the present invention would make them particularly suitable for corrective purposes besides replacements for diseased natural lenses and is considered within the scope of this invention. An unexpected, and beneficial, advantage of the present invention is the optically smooth surface formed after the lens has cured in situ.
The following examples are offered as being illustrative of the principles of the present invention and not by way of limitation.